10-105076813-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014978.3(SORCS3):​c.1029-12962G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,096 control chromosomes in the GnomAD database, including 36,333 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 36333 hom., cov: 32)

Consequence

SORCS3
NM_014978.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.377
Variant links:
Genes affected
SORCS3 (HGNC:16699): (sortilin related VPS10 domain containing receptor 3) This gene encodes a type-I receptor transmembrane protein that is a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined by a vacuolar protein sorting 10 domain at the N-terminus. The N-terminal segment of this domain has a consensus motif for proprotein convertase processing, and the C-terminal segment of this domain is characterized by ten conserved cysteine residues. The vacuolar protein sorting 10 domain is followed by a leucine-rich segment, a transmembrane domain, and a short C-terminal cytoplasmic domain that interacts with adaptor molecules. The transcript is expressed at high levels in the brain, and candidate gene studies suggest that genetic variation in this gene is associated with Alzheimer's disease. Consistent with this observation, knockdown of the gene in cell culture results in an increase in amyloid precursor protein processing. [provided by RefSeq, Dec 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SORCS3NM_014978.3 linkuse as main transcriptc.1029-12962G>T intron_variant ENST00000369701.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SORCS3ENST00000369701.8 linkuse as main transcriptc.1029-12962G>T intron_variant 1 NM_014978.3 P1

Frequencies

GnomAD3 genomes
AF:
0.689
AC:
104731
AN:
151978
Hom.:
36313
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.705
Gnomad AMI
AF:
0.591
Gnomad AMR
AF:
0.613
Gnomad ASJ
AF:
0.701
Gnomad EAS
AF:
0.836
Gnomad SAS
AF:
0.639
Gnomad FIN
AF:
0.795
Gnomad MID
AF:
0.674
Gnomad NFE
AF:
0.673
Gnomad OTH
AF:
0.694
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.689
AC:
104798
AN:
152096
Hom.:
36333
Cov.:
32
AF XY:
0.692
AC XY:
51459
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.705
Gnomad4 AMR
AF:
0.612
Gnomad4 ASJ
AF:
0.701
Gnomad4 EAS
AF:
0.836
Gnomad4 SAS
AF:
0.639
Gnomad4 FIN
AF:
0.795
Gnomad4 NFE
AF:
0.673
Gnomad4 OTH
AF:
0.689
Alfa
AF:
0.674
Hom.:
4924
Bravo
AF:
0.680
Asia WGS
AF:
0.677
AC:
2354
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.0
DANN
Benign
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs703460; hg19: chr10-106836571; API